The influenza virus PB1-F2 protein has interferon-antagonistic activity

Dudek, Sabine Eva; Wixler, Ludmilla; Nordhoff, Carolin; Nordmann, Alexandra; Anhlan, Darisuren; Wixler, Viktor; Ludwig, Stephan

doi:10.1515/bc-2011-174

Cited by 13 publications

(13 citation statements)

References 40 publications

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“…IAV also encodes several proteins (PB1-F2, PB2, PA, and M2) that have been identified as affecting the host's innate immune response to a certain degree. PB1-F2 blocks the IFN response by interacting directly with the components (RIG-I/MAVs protein complex) of the interferon pathway [65,66]. PB1-F2 also promotes the inflammatory response and contributes to viral virulence and the acquisition of secondary bacterial infections [67][68][69][70][71].…”

Section: Other Immunomodulatory Proteins In Influenza Virusesmentioning

confidence: 99%

PA-X: a key regulator of influenza A virus pathogenicity and host immune responses

Liu

2018

Med Microbiol Immunol

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PA-X, a fusion protein belonging to influenza A viruses (IAVs), integrating the N-terminal 191 amino acids of PA gene and the ribosomal frame-shifting product that lengthens out to 41 or 61 amino acids. Since its discovery in 2012, multiple functions have been attributed to this small protein, including a process, where wide-spread protein synthesis in infected host cells is shut down (called host shutoff), and viral replication, polymerase activity, viral-induced cell apoptosis, PA nuclear localization, and virulence are modulated. However, many of its proposed functions may be specific to strain, subtype, host, or cell line. In this review, we start by describing the well-defined global host-shutoff ability of PA-X and the potential mechanisms underlying it. We move on to the role played by PA-X in modulating innate and acquired immune responses in the host. We then systematically discuss the role played by PA-X in modulating the virulence of influenza viruses of different subtypes and host origins, and finish with a general overview of the research advances made in identifying the host cell partners that interact with PA-X. To uncover possible clues about the differential effects of PA-X in modulating viral virulence, we focus on systemically evaluating polymorphisms in PA-X from various viral subtypes and hosts, including avian and human H5N1, H5N6, H9N2, and H7N9 viruses. Finally, we conclude with a proposition regarding the possible future research directions for this important protein.

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Section: Other Immunomodulatory Proteins In Influenza Virusesmentioning

confidence: 99%

PA-X: a key regulator of influenza A virus pathogenicity and host immune responses

Liu

2018

Med Microbiol Immunol

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“…qRT-PCR reaction mix (Brilliant III SYBR Green QPCR Master Mix) was purchased from Agilent Technologies. Analysis was performed as described earlier (Dudek et al, 2010;Dudek et al, 2011).…”

Section: Standard Plaque Titrationmentioning

confidence: 99%

Phosphorylation of influenza A virus NS1 protein at threonine 49 suppresses its interferon antagonistic activity

Kathum

Schräder

Anhlan

et al. 2016

Cellular Microbiology

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SummaryPhosphorylation and dephosphorylation acts as a fundamental molecular switch that alters protein function and thereby regulates many cellular processes. The non‐structural protein 1 (NS1) of influenza A virus is an important factor regulating virulence by counteracting cellular immune responses against viral infection. NS1 was shown to be phosphorylated at several sites; however, so far, no function has been conclusively assigned to these post‐translational events yet. Here, we show that the newly identified phospho‐site threonine 49 of NS1 is differentially phosphorylated in the viral replication cycle. Phosphorylation impairs binding of NS1 to double‐stranded RNA and TRIM25 as well as complex formation with RIG‐I, thereby switching off its interferon antagonistic activity. Because phosphorylation was shown to occur at later stages of infection, we hypothesize that at this stage other functions of the multifunctional NS1 beyond its interferon‐antagonistic activity are needed.

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“…This polypeptide, or PB1-F2 has been implicated in the virulence of the virus, with specific polymorphisms, such as N66S, found in the 1918 human pandemic strain of influenza virus, associated with increased pathogenesis (Conenello et al, 2007;McAuley et al, 2010;McAuley et al, 2007;Schmolke et al, 2011). Interestingly, PB1-F2 has a mitochondrial localization signal, and in the mitochondria appears to inhibit IFN induction most likely by interacting with MAVS, a critical mitochondrial adaptor required for IFN induction by the RLR pathway (Dudek et al, 2011;Varga et al, 2011).…”

Section: The Pb1-f2 Proteinmentioning

confidence: 99%

Induction and evasion of type I interferon responses by influenza viruses

2011

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Influenza A and B viruses are a major cause of respiratory disease in humans. In addition, influenza A viruses continuously re-emerge from animal reservoirs into humans causing human pandemics every 10–50 years of unpredictable severity. Among the first lines of defense against influenza virus infection, the type I interferon (IFN) response plays a major role. In the last 10 years, there have been major advances in understanding how cells recognize being infected by influenza viruses, leading to secretion of type I IFN, and on the effector mechanisms by how IFN exerts its antiviral activity. In addition, we also now know that influenza virus uses multiple mechanisms to attenuate the type I IFN response, allowing for successful infection of their hosts. This review highlights some of these findings and illustrates future research avenues that might lead to new vaccines and antivirals based on the further understanding of the mechanisms of induction and evasion of type I IFN responses by influenza viruses.

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The influenza virus PB1-F2 protein has interferon-antagonistic activity

Cited by 13 publications

References 40 publications

PA-X: a key regulator of influenza A virus pathogenicity and host immune responses

PA-X: a key regulator of influenza A virus pathogenicity and host immune responses

Phosphorylation of influenza A virus NS1 protein at threonine 49 suppresses its interferon antagonistic activity

Induction and evasion of type I interferon responses by influenza viruses

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